Database Query Results : Berberine, ,

BBR, Berberine: Click to Expand ⟱
Features:
Berberine is a chemical found in some plants like European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Berberine is a bitter-tasting and yellow-colored chemical.
Coptis (commonly referring to Coptidis Rhizoma, a traditional Chinese medicinal herb) contains bioactive alkaloids (most notably berberine and coptisine) that have been studied for their pharmacological effects—including their influence on reactive oxygen species (ROS) and related pathways.

– Berberine is known for its relatively low oral bioavailability, often cited at less than 1%. This low bioavailability is mainly due to poor intestinal absorption and active efflux by transport proteins such as P-glycoprotein.
– Despite the low bioavailability, berberine is still pharmacologically active, and its metabolites may also contribute to its overall effects.

• Effective Dosage in Studies
– Many clinical trials or preclinical studies use dosages in the range of 500 to 1500 mg per day, typically administered in divided doses.
– Therefore, to obtain a bioactive dose of berberine, supplementation in a standardized extract form is necessary.

-IC50 in cancer cell lines: Approximately 10–100 µM (commonly around 20–50 µM in many models)
-IC50 in normal cell lines: Generally higher (often above 100 µM), although this can vary with cell type
- In vivo studies: Dosing regimens in animal models generally range from about 50 to 200 mg/kg
- very effective AChE inhibitor (Alzheimers)
- Berberine may enhance the effects of blood-thinning medications like warfarin and aspirin.


-Note half-life reports vary 2.5-90hrs?.
-low solubility of apigenin in water : BioAv
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, UPR↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, GSH↓
- Raises AntiOxidant defense in Normal Cells: NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- PI3K/AKT(Inhibition), JAK/STATs, Wnt/β-catenin, AMPK, MAPK/ERK, and JNK.
- inhibit Growth/Metastases : , MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, EZH2↓, P53↑, HSP↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, CD133↓, β-catenin↓, n-myc↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,
- Selectivity: Cancer Cells vs Normal Cells



Scientific Papers found: Click to Expand⟱
2693- BBR,    Antitumor Effects of Berberine on Gliomas via Inactivation of Caspase-1-Mediated IL-1β and IL-18 Release
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG
"highlight2" >Casp1↓, berberine significantly inhibits inflammatory cytokine Caspase-1 activation via ERK1/2 signaling and subsequent production of IL-1β and IL-18 by glioma cells.
"highlight2" >ERK↓, berberine induces senescence of human glioma cells by downregulating the extracellular kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway
"highlight2" >IL1β↓, Berberine Exhibit Inhibitory Effects on Caspase-1, IL-18, and IL-1β Proteins
"highlight2" >IL18↓,
"highlight2" >EMT↑, berberine can reverse the process of epithelial-mesenchymal transition. aken together, these results suggest that berberine can inhibit the process of EMT

2706- BBR,    Berberine Inhibits Growth of Liver Cancer Cells by Suppressing Glutamine Uptake
- in-vitro, HCC, Hep3B - in-vitro, HCC, Bel-7402 - in-vivo, NA, NA
"highlight2" >TumCP↓, Berberine inhibited the proliferation of Hep3B and BEL-7404 cell in vitro
"highlight2" >glut↓, Berberine suppressed the glutamine uptake by inhibiting SLC1A5.
"highlight2" >SLC12A5↓,
"highlight2" >cMyc↓, Berberine suppresses SLC1A5 expression by inhibiting c-Myc
"highlight2" >GLS↓, The expression of SLC1A5, GLS and PSPH decreased, and such decrease was enhanced with the increase in berberine dose

2705- BBR,    Mechanism underlying berberine's effects on HSP70/TNFα under heat stress: Correlation with the TATA boxes
- in-vivo, Nor, NA - in-vitro, Nor, PC12
"highlight2" >HSP70/HSPA5↓, BBR was capable of decreasing the expression of both HSP70 and TNFα
"highlight2" >TNF-α↓,

2704- BBR,    Inhibitory Effect of Berberine on Zeste Homolog 2 (Ezh2) Enhancement in Human Esophageal Cell Lines
- in-vitro, ESCC, KYSE450
"highlight2" >EZH2↓, Berberine-induced inhibition of Ezh2 expression led to inhibition of cell proliferation by G1 phase cell cycle arrest and induced anti-invasive properties of KYSE450 cells in Boyden chamber assays.
"highlight2" >AXL↓, Berberine treatment also resulted in strong transcriptional reduction of the AXL receptor kinase.

2703- BBR,  CUR,  SFN,  UA,  GamB  Naturally occurring anti-cancer agents targeting EZH2
- Review, Var, NA
"highlight2" >EZH2↓, In fact, several natural products such as curcumin, triptolide, ursolic acid, sulforaphane, davidiin, tanshindiols, gambogic acid, berberine and Alcea rosea have been shown to serve as EZH2 modulators.

2702- BBR,    The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1
- in-vitro, Lung, A549 - in-vitro, Lung, H1975
"highlight2" >TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
"highlight2" >MAPK↓,
"highlight2" >FOXO3↑,
"highlight2" >TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
"highlight2" >PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
"highlight2" >DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
"highlight2" >eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

2701- BBR,    Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice
- in-vivo, Diabetic, NA
"highlight2" >*Inflam↓, Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis
"highlight2" >*antiOx↑,
"highlight2" >*Ferroptosis↓,
"highlight2" >*RenoP↑, Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice.
"highlight2" >*DNMT1↓, Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation.
"highlight2" >*DNMTs↓,
"highlight2" >*KLF4↑,

2700- BBR,    Cell-specific pattern of berberine pleiotropic effects on different human cell lines
- in-vitro, GBM, U343 - in-vitro, GBM, MIA PaCa-2 - in-vitro, Nor, HDFa
"highlight2" >selectivity↑, berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF
"highlight2" >TumCCA↑, Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner.
"highlight2" >Casp3↑, it increases caspase-3 activity and impairs migration/invasion.
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >N-cadherin?,
"highlight2" >DNMT1↑, DNMT1 was also upregulated in U343 cells (4-fold) after 50 μM berberine for 48 hours and in MIA PaCa-2 cells after treatment with both 10 μM and 50 μM berberine for 48 hours (5-fold and 15-fold, respectively).

2699- BBR,    Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line
- in-vitro, Lung, A549
"highlight2" >HDAC↓, BBR represses total HDAC and also class I, II, and IV HDAC activity through hyperacetylation of histones.
"highlight2" >TumCCA↑, BBR triggers positive regulation of the sub-G0/G1 cell cycle progression phase in A549 cells.
"highlight2" >TNF-α↓, BBR downregulates oncogenes (TNF-α, COX-2, MMP-2, and MMP-9) and upregulates tumor suppressor genes (p21 and p53) mRNA and protein expressions.
"highlight2" >COX2↓,
"highlight2" >MMP2↓, BBR Induces Downregulation of MMP-2 and MMP-9
"highlight2" >MMP9↓,
"highlight2" >P21↑,
"highlight2" >P53↑,
"highlight2" >Casp↑, triggered the caspase cascade apoptotic pathway in A549 cells
"highlight2" >ac‑H3↑, BBR Increases the Acetylation State of Histones H3 and H4.
"highlight2" >ac‑H4↑,
"highlight2" >ROS↑, BBR Induces ROS Generation, Δψm Alteration, Membrane Loss, and Nuclear Fragmentation
"highlight2" >MMP↓,

2698- BBR,    A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine
- Analysis, BC, MDA-MB-231
"highlight2" >HDAC↓, Results showed that BBR may inhibit protein synthesis, histone deacetylase (HDAC), or AKT/mammalian target of rapamycin (mTOR) pathways.
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >ER Stress↑, BBR inhibited global protein synthesis and basal AKT activity, and induced endoplasmic reticulum (ER) stress and autophagy, which was associated with activation of AMP-activated protein kinase (AMPK).
"highlight2" >TumAuto↑,
"highlight2" >AMPK↑,
"highlight2" >mTOR∅, However, BBR did not alter mTOR or HDAC activities.
"highlight2" >HDAC∅, SAHA but not BBR inhibited HDAC activity, suggesting that BBR is not an HDAC inhibitor.
"highlight2" >ac‑α-tubulin↑, BBR induced the acetylation of α-tubulin, a substrate of HDAC6, although it did not directly inhibit HDAC activity

2697- BBR,    Structural exploration of common pharmacophore based berberine derivatives as novel histone deacetylase inhibitor targeting HDACs enzymes
- Analysis, Var, NA
"highlight2" >HDAC↓, We derived four berberine derivatives based on common HDAC inhibition pharmacophore

2696- BBR,    Berberine regulates proliferation, collagen synthesis and cytokine secretion of cardiac fibroblasts via AMPK-mTOR-p70S6K signaling pathway
- in-vivo, Nor, NA
"highlight2" >*α-SMA↓, It was demonstrated that treatment of cardiac fibroblasts with berberine resulted in deceased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen synthesis.
"highlight2" >*TGF-β1↓, protein secretion of TGFβ1 was inhibited; however, the protein secretion of IL-10 was increased in cardiac fibroblasts with berberine treatment.
"highlight2" >*IL10↑,
"highlight2" >*p‑AMPK↑, Mechanistically, the phosphorylation level of AMPK was increased
"highlight2" >*p‑mTOR↓, phosphorylation levels of mTOR and p70S6K were decreased in berberine treatment group
"highlight2" >*P70S6K↓,
"highlight2" >*cardioP↑, protective effects of berberine on cellular behaviors of cardiac fibroblasts

2695- BBR,    The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial
- Trial, BC, NA
"highlight2" >IGF-1↓, BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD.
"highlight2" >PPARγ↓, The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis.
"highlight2" >VEGF↓,
"highlight2" >Hif1a↓, down-regulating effects of BV juice on PPAR-γ, VEGF, and HIF-1α
"highlight2" >angioG↓, berberine can decrease angiogenesis and related biomarkers including VEGF in breast cancer cells

2694- BBR,    Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells
- in-vitro, BC, NA
"highlight2" >IL8↓, BBR dramatically suppresses IL-8 expression.
"highlight2" >TumCI↓, BBR also inhibited cell invasiveness
"highlight2" >EGFR↓, BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation.
"highlight2" >MEK↓,
"highlight2" >ERK↓,
"highlight2" >TGF-β1↓, BBR inhibits the tumorigenic and angiogenic properties of TNBC cells by inhibiting TGF-β1 expression and VEGF secretion (
"highlight2" >VEGF↓,

2707- BBR,    Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
"highlight2" >GLUT1↓, BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1
"highlight2" >Akt↓, and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines
"highlight2" >mTOR↓,
"highlight2" >ATP↓, BBR-induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation
"highlight2" >GlucoseCon↓,
"highlight2" >TumCP↓,
"highlight2" >Warburg↓, antineoplastic effect of BBR may involve the reversal of the Warburg effect
"highlight2" >selectivity↑, The results demonstrated that the colony-forming capacity was slightly inhibited in Hs 578Bst normal breast cells following BBR treatment, but significantly inhibited in both cancer cell lines.
"highlight2" >TumCCA↑, BBR effectively induced cell cycle arrest at the G2M phase
"highlight2" >Glycolysis↓, Notably, our preliminary experiments identified that BBR strongly decreased the glucose uptake ability of HepG2 and MCF7 cell lines, therefore, it was hypothesized that BBR may interfere with tumor progression by inhibiting glycolysis.

2692- BBR,    Berberine affects osteosarcoma via downregulating the caspase-1/IL-1β signaling axis
- in-vitro, OS, MG63 - in-vitro, OS, SaOS2 - in-vivo, NA, NA
"highlight2" >Casp1↓, administration of berberine is capable of reducing the expression of caspase-1 and IL-1β in osteosarcoma cells and inhibiting the growth of tumor cells.
"highlight2" >IL1β↓,
"highlight2" >TumCG↓,
"highlight2" >Dose↝, concentration of berberine at 80 µM could inhibit the cell viability to the greatest extent; and the viable cells at 48 h decreased more obviously than 24 h after treatment with 80 µM berberine.
"highlight2" >Apoptosis↑, Berberine induces apoptosis of Saos-2 and MG-63 osteosarcoma cells
"highlight2" >Inflam↓, these observations demonstrate that berberine could probably relieve the inflammation in tumor microenvironment and then results in apoptosis of osteosarcoma cells.

2691- BBR,    Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells
- in-vitro, Oral, KB
"highlight2" >tumCV↓, viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner.
"highlight2" >DNAdam↑, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation.
"highlight2" >Casp3↑, caspase-3 and -7 activation, and an increase in apoptosis were observed.
"highlight2" >Casp7↑,
"highlight2" >FasL↑, Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL
"highlight2" >Casp8↑, triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP).
"highlight2" >Casp9↑,
"highlight2" >PARP↑,
"highlight2" >BAX↑, Bax, Bad and Apaf-1 were also significantly upregulated by berberine.
"highlight2" >BAD↑,
"highlight2" >APAF1↑,
"highlight2" >MMP2↓, We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK.
"highlight2" >MMP9↓,
"highlight2" >p‑p38↑, This suggests that berberine-induced activation of the p38 and ERK1/2 MAPK pathways is the principal pathway involved in the apoptosis mediated by berberine in KB cells.
"highlight2" >ERK↑,
"highlight2" >MAPK↑,

2690- BBR,    Berberine Differentially Modulates the Activities of ERK, p38 MAPK, and JNK to Suppress Th17 and Th1 T Cell Differentiation in Type 1 Diabetic Mice
- in-vivo, Diabetic, NA
"highlight2" >*Inflam↓, Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation.
"highlight2" >*Th17↓, Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion.
"highlight2" >*Th1 response↓,
"highlight2" >*ERK↑, berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation.
"highlight2" >*p38↓,
"highlight2" >*JNK↓,
"highlight2" >*STAT1↓, Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation,
"highlight2" >*STAT4↓,
"highlight2" >*MAPK↓,

2689- BBR,    Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells
- in-vitro, Nor, PC12 - in-vitro, AD, NA - in-vitro, Stroke, NA
"highlight2" >*ROS↓, In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells.
"highlight2" >*lipid-P↓,
"highlight2" >*DNAdam↓, Berberine significantly diminished glutamate-induced DNA fragmentation
"highlight2" >*GSH↑,
"highlight2" >*SOD↑,
"highlight2" >*eff↑, This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer’s disease), seizures, and stroke.
"highlight2" >*cl‑Casp3↓, Berberine significantly decreased cleaved caspase-3 and bax/bcl-2 expressions in the glutamate-injured cells
"highlight2" >*BAX↓,
"highlight2" >*neuroP↑, the current study demonstrated that berberine exerts neuroprotective effects against glutamate-induced N2a and PC12 cytotoxicity via antioxidant and anti-apoptotic mechanisms
"highlight2" >*Dose↝, the protective effect of berberine was more significant at lower concentrations and decreased with increasing concentration.
"highlight2" >*Ca+2↓, Nadjafi et al demonstrated that berberine protects OLN-93 oligodendrocytes against ischemic-induced cell death by attenuating the intracellular Ca2+ overload similar to the NMDA or the AMPA/kainate receptors antagonists

2686- BBR,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, Nor, NA
"highlight2" >Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
"highlight2" >IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
"highlight2" >MCP1↓,
"highlight2" >COX2↓,
"highlight2" >PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
"highlight2" >MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
"highlight2" >MMP9↓,
"highlight2" >DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
"highlight2" >eff↝, In some cell types, this response has been reported to be TP53-dependent
"highlight2" >Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
"highlight2" >Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
"highlight2" >AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
"highlight2" >ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
"highlight2" >MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
"highlight2" >ATP↓,
"highlight2" >p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
"highlight2" >p‑S6K↓,
"highlight2" >ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
"highlight2" >PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
"highlight2" >PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
"highlight2" >Akt↓,
"highlight2" >Raf↓,
"highlight2" >MEK↓,
"highlight2" >Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
"highlight2" >Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
"highlight2" >selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
"highlight2" >TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
"highlight2" >eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
"highlight2" >EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
"highlight2" >Glycolysis↓, accompanied by impaired glycolytic capacity.
"highlight2" >Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
"highlight2" >p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >cycD1↓,
"highlight2" >cycE↓,
"highlight2" >Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
"highlight2" >Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
"highlight2" >Casp9↑,
"highlight2" >VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
"highlight2" >ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
"highlight2" >eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
"highlight2" >eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
"highlight2" >PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
"highlight2" >JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
"highlight2" >STAT3↓,
"highlight2" >CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
"highlight2" >CCR7↓,
"highlight2" >uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
"highlight2" >CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
"highlight2" >EMT↓,
"highlight2" >Diff↓,
"highlight2" >CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
"highlight2" >Nestin↓,
"highlight2" >n-MYC↓,
"highlight2" >NOTCH↓,
"highlight2" >SOX2↓,
"highlight2" >Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
"highlight2" >VEGF↓,
"highlight2" >RadioS↑,

2685- BBR,    Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells
- in-vitro, neuroblastoma, NA
"highlight2" >CSCs↓, Berberine attenuated cancer stemness markers CD133, β-catenin, n-myc, sox2, notch2 and nestin.
"highlight2" >CD133↓,
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >n-MYC↓,
"highlight2" >SOX2↓,
"highlight2" >NOTCH2↓,
"highlight2" >Nestin↓,
"highlight2" >TumCCA↑, Berberine potentiated G0/G1 cell cycle arrest by inhibiting proliferation, cyclin dependent kinases and cyclins resulting in apoptosis through increased bax/bcl-2 ratio.
"highlight2" >TumCP↓,
"highlight2" >CDK1↓,
"highlight2" >Cyc↓,
"highlight2" >Apoptosis↑,
"highlight2" >Bax:Bcl2↑,
"highlight2" >NCAM↓, The induction of NCAM and reduction in its polysialylation indicates anti-migratory potential which is supported by down regulation of MMP-2/9.
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >*Smad1↑, It increased epithelial marker laminin and smad and increased Hsp70 levels also suggest its protective role.
"highlight2" >*HSP70/HSPA5↑,
"highlight2" >*LAMs↑,

2684- BBR,    Berberine is a Novel Mitochondrial Calcium Uniporter Inhibitor that Disrupts MCU‐EMRE Assembly
- in-vivo, Nor, NA
"highlight2" >*MCU↓, These findings establish Berberine as a potent MCU inhibitor, offering a safe therapeutic strategy for diseases associated with dysregulated mitochondrial calcium homeostasis.
"highlight2" >*mt-Ca+2↓, Berberine pretreatment reduces mitochondrial Ca2+ overload and mitigates ischemia/reperfusion‐induced myocardial injury in mice.
"highlight2" >*cardioP↑, Berberine significantly reduces mitochondrial Ca2+ overload, providing cardioprotection against I/R‐induced myocardial injury in mice.

2683- BBR,    Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells
- in-vitro, Liver, HepG2
"highlight2" >JNK↓, while the activation of JNK was blocked
"highlight2" >p‑PERK↓, phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine.
"highlight2" >p‑eIF2α↓,
"highlight2" >*ER Stress↓, antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress

2682- BBR,    Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions
- in-vitro, CRC, HT29 - in-vitro, CRC, SW480 - in-vitro, CRC, HCT116
"highlight2" >TumCP↓, We demonstrated that treatment of these CRC cell lines with berberine inhibited cell proliferation, migration and invasion through induction of apoptosis and necrosis.
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >Apoptosis↑,
"highlight2" >necrosis↑,
"highlight2" >AQPs↓, berberine treatment down-regulated the expression of all three types of AQPs.
"highlight2" >PTEN↑, up-regulating PTEN and down-regulating PI3K, AKT and p-AKT expression as well as suppressing its downstream targets, mTOR and p-mTOR at the protein level
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >p‑Akt↓,
"highlight2" >mTOR↓,
"highlight2" >p‑mTOR↓,

2681- BBR,  PDT,    Berberine-photodynamic induced apoptosis by activating endoplasmic reticulum stress-autophagy pathway involving CHOP in human malignant melanoma cells
- in-vitro, Melanoma, NA
"highlight2" >Apoptosis↑, BBR-PDT induced apoptosis via up-regulating the expression of cleaved caspase-3 protein.
"highlight2" >cl‑Casp3↑,
"highlight2" >LC3s↑, LC3-related autophagy level was upregulated in MMCs with BBR-PDT.
"highlight2" >ER Stress↑, BBR-PDT activated endoplasmic reticulum (ER) stress, involving a dramatic increase in reactive oxygen species (ROS).
"highlight2" >ROS↑,
"highlight2" >CHOP↑, knockdown of CHOP protein expression inhibited apoptosis, autophagy and ER stress levels caused by BBR-PDT, suggesting that CHOP protein may be related to apoptosis, autophagy and ER stress in MMCs with BBR-PDT

2680- BBR,  PDT,    Photodynamic therapy-triggered nuclear translocation of berberine from mitochondria leads to liver cancer cell death
- in-vitro, Liver, HUH7
"highlight2" >TumCD↑, blue light irradiation (488 nm). The results showed that berberine rapidly translocated from the mitochondria to the nucleus upon light exposure, ultimately inducing cell death in SNU449 and Huh7 cells.
"highlight2" >ROS↑, Additionally, we observed a significant increase in reactive oxygen species, linking the phototoxic effects to oxidative stress
"highlight2" >TumCCA↑, indicating cell cycle arrest following treatment with berberine and PDT
"highlight2" >ER Stress↑, Western blotting confirmed that ER stress was significantly induced

2679- BBR,    Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer’s Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress
- in-vivo, AD, NA
"highlight2" >*cognitive↑, berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer’s disease (3 × Tg AD) mice.
"highlight2" >PERK↓, berberine treatment may inhibit PERK/eIF2α signaling-mediated BACE1 translation, thus reducing Aβ production and resultant neuronal apoptosis
"highlight2" >*eIF2α↓,
"highlight2" >*neuroP↑, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress.
"highlight2" >*ER Stress↓,
"highlight2" >*ROS↓,

3680- BBR,    Network pharmacology reveals that Berberine may function against Alzheimer’s disease via the AKT signaling pathway
- in-vivo, AD, NA
"highlight2" >*Akt↑, Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05).
"highlight2" >*neuroP↑, BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways.
"highlight2" >*p‑ERK↑, Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels.
"highlight2" >*Aβ↓, BBR has therapeutic potential in the treatment of AD by targeting amyloid beta plaques, neurofibrillary tangles, neuroinflammation, and oxidative stress
"highlight2" >*Inflam↓,
"highlight2" >*ROS↓,
"highlight2" >*BioAv↑, oral bioavailability (OB) = 36.86%, drug-likeness (DL) = 0.78,
"highlight2" >*BBB↑, blood brain barrier (BBB) = 0.57,
"highlight2" >*Half-Life↝, half-life (HL) = 6.57. BBR half-life (t1/2) is in the mid-elimination group.
"highlight2" >*memory↑, BBR improves the performance of memory and recognition tasks in AD mice
"highlight2" >*cognitive↑,
"highlight2" >*HSP90↑, Among the core targets, Akt1 (t = −5.01, p = 0.002), Hsp90aa1 (t = −3.66, p = 0.011), Hras (t = −2.99, p = 0.024) and Igf1 (t = 3.75, p = 0.019) mRNA levels were significantly increased after BBR treatment
"highlight2" >*APP↓, BBR reduces Aβ levels by modulating APP processing and ameliorates Aβ pathology by inhibiting the mTOR/p70S6K signaling pathway
"highlight2" >*mTOR↓,
"highlight2" >*P70S6K↓,
"highlight2" >*CD31↑, it promotes the formation of brain microvessels by enhancing CD31, VEGF, N-cadherin, Ang-1 and inhibits neuronal apoptosis (Ye et al., 2021).
"highlight2" >*VEGF↑,
"highlight2" >*N-cadherin↑,
"highlight2" >*Apoptosis↓,

4340- BBR,    Agonist-dependent differential effects of berberine in human platelet aggregation
- Human, NA, NA
"highlight2" >*AntiAg↑, berberine selectively inhibits collagen-induced platelet aggregation
"highlight2" >*other?, Since berberine was unable to inhibit the aggregation mediated by activation of thromboxane A2, increase in calcium influx, or stimulation of G-protein linked pathways, it is likely that berberine selectively inhibits platelet aggregation by interfer

4300- BBR,    Effect of berberine on cognitive function and β-amyloid precursor protein in Alzheimer’s disease models: a systematic review and meta-analysis
- Review, AD, NA
"highlight2" >*APP↓, Berberine can regulate APP expression and improve cognitive function in animal models of AD,
"highlight2" >*cognitive↑,
"highlight2" >*Aβ↓, Berberine is involved in regulating APP modification, which may inhibit Aβ production through BACE1 inhibition and regulation of γ-secretase substrates.
"highlight2" >*BACE↓,
"highlight2" >*tau?, berberine may be a good multi-targeted drug that can modulate AD related substances tau, PP-2A, Aβ, APP, or BACE-2.

4299- BBR,    Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation
- in-vivo, AD, NA
"highlight2" >*memory↑, BBR improved learning and memory in APP/PS1 mice.
"highlight2" >*p‑tau↓, BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice.
"highlight2" >*NF-kB↓, BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice.
"highlight2" >*GSH↑, BBR-administration promoted the activity of glutathione (GSH) and inhibited lipid peroxidation in the hippocampus of AD mice.
"highlight2" >*lipid-P↓,
"highlight2" >*cognitive↑, BBR attenuated cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB
"highlight2" >*ROS↓, by retarding oxidative stress and neuro-inflammation.
"highlight2" >*Inflam↓,

4298- BBR,    Berberine mitigates cognitive decline in an Alzheimer’s Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
- in-vivo, AD, NA
"highlight2" >*cognitive↑, Berberine could improve 3×Tg AD mice’s cognitive function
"highlight2" >*p‑tau↓, Berberine could attenuate the hyperphosphorylation of tau
"highlight2" >*GSK‐3β↓, attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A
"highlight2" >*PP2A↑, inhibition of GSK3β or activation of PP2A attenuates tau hyperphosphorylation, thus, ameliorates cognitive impairment
"highlight2" >*memory↑, Berberine-treated mice showed better performance in spatial learning and memory test
"highlight2" >*Akt↑, Berberine decreases tau phosphorylation via activation of Akt and inhibition of GSK3β
"highlight2" >*LC3II↑, both LC3-Ⅱ and Beclin-1 in the hippocampus of BBR-treated group were dramatically increased compared with the 3×Tg AD mice
"highlight2" >*Beclin-1↑,

4275- BBR,    Pharmacological effects of berberine on mood disorders
- Review, NA, NA
"highlight2" >*antiOx↑, Berberine has multiple therapeutic actions, including antioxidant, anti‐inflammatory, antitumour, antimicrobial, hepatoprotective, hypolipidemic, and hypoglycemic actions.
"highlight2" >*Inflam↓,
"highlight2" >*hepatoP↑,
"highlight2" >*eff↑, recent studies show that berberine has a protective effect on central nervous system disorders, such as Alzheimer's, cerebral ischaemia, mental depression, schizophrenia, and anxiety
"highlight2" >*5HT↑, Chronic administration of berberine (5 mg/kg, ip) for 15 days significantly increased the levels of norepinephrine (29%), serotonin (19%) as well as dopamine (52%)
"highlight2" >*Mood↑, An antidepressant effect of berberine results from elevation of brain‐derived neurotrophic factor (BDNF) levels.
"highlight2" >*BDNF↑,

4274- BBR,    Berberine exerts antidepressant effects in vivo and in vitro through the PI3K/AKT/CREB/BDNF signaling pathway
- in-vivo, NA, NA
"highlight2" >*IL1β↓, serum levels of IL-1β, IL-6, TNF-α and CRP in CRS mice were significantly increased, while berberine and fluoxetine could down-regulate the expression of the above cytokines.
"highlight2" >*IL6↓,
"highlight2" >*TNF-α↓,
"highlight2" >*CRP↓,
"highlight2" >*CREB↑, The results showed that the mRNA and protein expression (or phosphorylation) levels of CREB (Fig. 4B, D) and BDNF (Fig. 4C, E) were decreased in the hippocampus of CRS mice, which could be reversed by berberine treatment
"highlight2" >*BDNF↑,

3833- BBR,    Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer’s Disease
- Review, AD, NA
"highlight2" >*cardioP↑, used to manage cardiovascular and neurodegenerative diseases
"highlight2" >*neuroP↑,
"highlight2" >*memory↑, Ber improves memory retention and spatial learning capacity by promoting Aβ clearance.
"highlight2" >*Aβ↓,

3754- BBR,  CUR,  EGCG,  Hup,    Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer’s disease: A review
"highlight2" >*AChE↓, Berberine (9) has gained considerable attention due to its wide pharmacological potentials and several biological properties, such as acetylcholinesterase and butyrylcholinesterase inhibitory, antioxidant, monoamine oxidase oxidase,
"highlight2" >*Aβ↓, amyloid-b peptide level-reducing, cholesterol- lowering and renoprotective activities
"highlight2" >*LDL↓,
"highlight2" >*RenoP↑,
"highlight2" >*BChE↓,
"highlight2" >*eff↑, Above all, the berberine-pyrocatechol hybrid (14) showed a strong AChE inhibitor activity (IC50 of 123 ± 3 nM) [34]
"highlight2" >*BACE↓, Curcumin: inhibite the rBACE1 activity [42]. In addition, it has made good inhibitory effect on acetylcholinesterase activity
"highlight2" >*AChE↓, EGCG promoted brain health, prevented AD progression, and inhibited the AChE activity [52,53].
"highlight2" >*eff↑, EGCG could enhance the effect of huperzine A on inhibiting AChE.

3749- BBR,    Anti-Alzheimer and Antioxidant Activities of Coptidis Rhizoma Alkaloids
- Review, AD, NA
"highlight2" >*antiOx↑, Thus, the anti-Alzheimer and antioxidant effects of six protoberberine alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine)
"highlight2" >*AChE↓, Six protoberberine alkaloids exhibited predominant cholinesterases (ChEs) inhibitory effects with IC50 values ranging between 0.44—1.07 μM for AChE and 3.32—6.84 μM for BChE;
"highlight2" >*BChE?,

3684- BBR,    Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies
- Review, AD, NA
"highlight2" >*Inflam↓, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects.
"highlight2" >*antiOx↓,
"highlight2" >*AChE↓,
"highlight2" >*BChE↓, berberine exerts inhibitory effects on the four key enzymes in the pathogenesis of AD: acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A, and monoamine oxidase B
"highlight2" >*MAOA↓,
"highlight2" >*MAOB↓,
"highlight2" >*lipid-P↓, Fig3
"highlight2" >*GSH↑,
"highlight2" >*ROS↓,
"highlight2" >*APP↓,
"highlight2" >*BACE↓,
"highlight2" >*p‑tau↓,
"highlight2" >*NF-kB↓,
"highlight2" >*TNF-α↓,
"highlight2" >*IL1β↓,
"highlight2" >*MAPK↓,
"highlight2" >*PI3K↓,
"highlight2" >*Akt↓,
"highlight2" >*neuroP↑, neuroprotective effects of berberine have been extensively studied
"highlight2" >*memory↑, berberine displayed significant effects in preventing memory impairment in these mechanistically different animal models, suggesting an over-all improvement of memory function by berberine

3683- BBR,    Characterization of the anti-AChE potential and alkaloids in Rhizoma Coptidis from different Coptis species combined with spectrum-effect relationship and molecular docking
- NA, AD, NA
"highlight2" >*AChE↓, columbamine, berberine and palmatine were the most important AChE inhibitors that could be used as quality markers to select RC drugs for Alzheimer’s disease treatment.

3682- BBR,    Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer’s Disease
- in-vitro, AD, NA
"highlight2" >*cognitive↑, results showed that BBR ameliorated cognitive deficits in 3×Tg AD mice, reduced the Aβ accumulation, inhibited the apoptosis of neurons
"highlight2" >*Aβ↓,
"highlight2" >*Apoptosis↓,
"highlight2" >*CD31↑, promoted the formation of microvessels in the mouse brain by enhancing brain CD31, VEGF, N-cadherin, Ang-1.
"highlight2" >*VEGF↑,
"highlight2" >*N-cadherin↑,
"highlight2" >*angioG↑,
"highlight2" >*neuroP↑, berberine is effective to 3×Tg AD mice, has a neuroprotective effect,
"highlight2" >*p‑tau↓, lowering Aβ levels, inhibiting the phosphorylation of Tau protein, anti-oxidation, inhibiting the activity of AchE and MAO, and regulating lipids, hypoglycemic.
"highlight2" >*antiOx↑,
"highlight2" >*AChE↓,
"highlight2" >*MAOB↓,
"highlight2" >*lipid-P↓,

3681- BBR,    The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology
- in-vivo, AD, NA
"highlight2" >*memory↑, treatment with berberine significantly improved spatial learning and memory in mice with cognitive decline induced by D-gal
"highlight2" >*cognitive↑,
"highlight2" >MAPK↑, core targets of berberine for improving cognitive function, include Mapk1, Src, Ctnnb1, Akt1, Pik3ca, Tp53, Jun, and Hsp90aa1.
"highlight2" >*Akt↑,
"highlight2" >*PI3K↑, PI3K-Akt signaling pathway and MAPK signaling pathway were significantly enriched.
"highlight2" >*TP53↑, Tp53 and Jun expression showed a decreasing trend and were significantly lower in the BBR-H group
"highlight2" >*Jun↓,
"highlight2" >*HSP90↑, src, Ctnnb1, Akt1, Pik3ca, and Hsp90aa1 exhibited an increasing tendency in both the BBR-L and BBR-H groups
"highlight2" >*neuroP↑, Akt1, Ctnnb1, Tp53, and Jun were involved in the neuroprotective actions of berberine.
"highlight2" >*Inflam↓, pharmacological effects of BBR, including anti-inflammatory
"highlight2" >*antiOx↑, BBR has antioxidant properties as well as protective effects against neurodegenerative diseases
"highlight2" >*p16↓, BBR reduces the expression of P16 in brain tissue of cognitive dysfunctions mice
"highlight2" >*ER Stress↓, inhibition of endoplasmic reticulum stress

2678- BBR,    Berberine as a Potential Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
"highlight2" >*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
"highlight2" >*antiOx↑,
"highlight2" >*cardioP↑,
"highlight2" >*neuroP↑,
"highlight2" >TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
"highlight2" >cycD1↓,
"highlight2" >cycE↓,
"highlight2" >CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
"highlight2" >AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
"highlight2" >mTOR↝,
"highlight2" >Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
"highlight2" >Casp9↑,
"highlight2" >Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
"highlight2" >TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
"highlight2" >TumCI↓,
"highlight2" >EMT↓,
"highlight2" >MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
"highlight2" >E-cadherin↓,
"highlight2" >Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
"highlight2" >*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
"highlight2" >GRP78/BiP↓, Downregulates GRP78
"highlight2" >EGFR↓, Downregulates EGFR
"highlight2" >CDK4↓, downregulates CDK4, TERT, and TERC
"highlight2" >COX2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
"highlight2" >PGE2↓,
"highlight2" >p‑JAK2↓,
"highlight2" >p‑STAT3↓,
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
"highlight2" >eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
"highlight2" >*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
"highlight2" >BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)

3679- BBR,    Berberine alleviates Alzheimer's disease by activating autophagy and inhibiting ferroptosis through the JNK-p38MAPK signaling pathway
- in-vivo, AD, NA
"highlight2" >*Beclin-1↑, autophagy-related markers Beclin1 and LC3B were upregulated and P62 was downregulated after BBR treatment.
"highlight2" >*LC3B↑,
"highlight2" >*p62↓,
"highlight2" >*ROS↓, ROS and lipid peroxide MDA decreased significantly after BBR treatment.
"highlight2" >*lipid-P↓,
"highlight2" >*MDA↓,
"highlight2" >*Ferroptosis↓, expression levels of ferroptosis-related genes TFR1, ASCL4, DMT1, and IREB2 were decreased, while the expression levels of FTH1 and SLC7A11 increased after BBR treatment.
"highlight2" >*TfR1/CD71↓,
"highlight2" >*FTH1↑,
"highlight2" >*memory↑, BBR treatment enhanced spatial memory impairment in 5xFAD mice.
"highlight2" >*JNK↓, inhibited ferroptosis by inhibiting the JNK-P38MAPK signaling pathway.
"highlight2" >*p38↓,
"highlight2" >*Aβ↓, further reducing Aβ plaque deposition, inhibiting inflammatory response,
"highlight2" >*Inflam↓,

3678- BBR,    Network pharmacology study on the mechanism of berberine in Alzheimer’s disease model
- Review, AD, NA
"highlight2" >*APP↓, BBR were decreased in the mRNA and protein expression of APP and presenilin 1 while PPARG was increased with a reduction in the NF-κB pathway.
"highlight2" >*PPARγ↑, upregulated PPARG with decreasing its downstream NF-ΚB pathway
"highlight2" >*NF-kB↓,
"highlight2" >*Aβ↓, BBR played a protective role in the AD mice model via blocking APP processing and amyloid plaque formation.
"highlight2" >*cognitive↑, berberine significantly reduced amyloid accumulation and improved cognitive impairment in APP/PS1 mice
"highlight2" >*antiOx↑, via anti-oxidative stress, anti-neuroinflammation, inhibition of neuronal cell apoptosis, etc
"highlight2" >*Inflam↓,
"highlight2" >*Apoptosis↓,
"highlight2" >*BioAv↑, BBR was found to be metabolized to dihydro-berberine by intestinal bacteria, whose bioavailability was five times higher than that of BBR
"highlight2" >*BioAv↝, oral bioavailability (OB, >30%),
"highlight2" >*BBB↑, blood-brain barrier (BBB, >0.3)
"highlight2" >*motorD↑, BBR treated 5×FAD mice ameliorated their behavior activity including in locomotor activity and cognitive function compared to control.
"highlight2" >*NRF2↑, BBR enhanced cellular antioxidant capacity, regulated antioxidant-related pathways such as Nrf2 and HO-1, and thereby reduced oxidative stress damage
"highlight2" >*HO-1↑,
"highlight2" >*ROS↓,
"highlight2" >*p‑Akt↑, BBR significantly increased the phosphorylation levels of AKT and ERK
"highlight2" >*p‑ERK↑,

3677- BBR,    Berberine: A Potential Multipotent Natural Product to Combat Alzheimer’s Disease
- Review, AD, NA
"highlight2" >*antiOx↑, multiple activities of berberine, including antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory,
"highlight2" >*AChE↓, inhibit AChE with an IC50 of 0.44 μM
"highlight2" >*BChE↓, BChE inhibitor and the corresponding IC50 was estimated to be 3.44 μM
"highlight2" >*MAOA↓, inhibitory activity on MAO-A with an IC50 value of 126 μM
"highlight2" >*Aβ↓, monoamine oxidase inhibitory, amyloid-b peptide level-reducing and cholesterol-lowering activities.
"highlight2" >*LDL↓, effectively reduce serum cholesterol and LDL-cholesterol levels in hyperlipidemic hamsters and human hypercholesterolemic patients
"highlight2" >*ROS↓, First, it was reported that berberine can scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS)
"highlight2" >*RNS↓,
"highlight2" >*lipid-P↓, Secondly, berberine can inhibit lipid peroxidation
"highlight2" >*Dose↝, berberine can inhibit AChE with an IC50 of 0.44 μM
"highlight2" >*MAOB↓, inhibition of berberine against MAO-B: IC50 was estimated to be 98.4 μM
"highlight2" >*memory↑, beneficial effect of berberine in ameliorating memory dysfunction in a rat model of streptozotocin-induced diabetes
"highlight2" >*toxicity↓, Berberine is generally considered to be non-toxic at doses used in clinical situations and lacks genotoxic, cytotoxic or mutagenic activity
"highlight2" >*BBB↑, Berberine can be administered orally [67] and pass through the blood-brain barrier

3633- BBR,  LT,  Croc,  QC,    Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy
- Review, AD, NA
"highlight2" >*AChE↓, Alzheimer's disease (AD) is a main cause of dementia, accounting for up to 75% of all dementia cases. Pathophysiological processes described for AD progression involve neurons and synapses degeneration, mainly characterized by cholinergic impairment.
"highlight2" >*AChE↓, Fig1: Berberine(1uM), Luteolin(80uM), Crocetin(100uM), Quercetin(120uM)

2715- BBR,  Rad,    Berberine Can Amplify Cytotoxic Effect of Radiotherapy by Targeting Cancer Stem Cells
- in-vitro, BC, MCF-7
"highlight2" >tumCV↓, IR and berberine treatment decreased the viability of MCF-7 spheroids and reduced OCT4 and SOX2 genes expression.
"highlight2" >OCT4↓,
"highlight2" >SOX2↓,
"highlight2" >RadioS↑, Berberine has a radiosensitizing effect through targeting cancer stem cells
"highlight2" >CSCs↓,

2714- BBR,    Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer
"highlight2" >AMPK↑, Long term AMPK activation (24 h) with berberine induced β1 integrin degradation and impaired cell migration.
"highlight2" >ITGB1↓,

2713- BBR,    Berberine improved the microbiota in lung tissue of colon cancer and reversed the bronchial epithelial cell changes caused by cancer cells
- in-vitro, Nor, BEAS-2B
"highlight2" >*GutMicro↑, Berberine or probiotics significantly increased the alpha diversity of the lung microbiota
"highlight2" >*IL6↑, Berberine increased IL-6 and IL-10 and decreased IL-17 and IFN-γ expression in lung tissue
"highlight2" >*IL10↑,
"highlight2" >*IL17↑,
"highlight2" >*IFN-γ↑,
"highlight2" >PDGF↓, In addition, HT29 and RKO CM had no significant effect on the expression of PDGF-β in BEAS-2B cells, while berberine significantly reduced its expression.
"highlight2" >*RAD51↓, berberine protects lung cells against this stress by enhancing RAD51 expression.

2712- BBR,    Suppression of colon cancer growth by berberine mediated by the intestinal microbiota and the suppression of DNA methyltransferases (DNMTs)
- in-vitro, Colon, HT29 - in-vivo, NA, NA
"highlight2" >TumCG↓, BBR reduced the growth of colon cancer cells to a certain extent in vitro and in vivo,
"highlight2" >GutMicro↑, BBR significantly mediated the abundance, composition and metabolic functions of the intestinal microbial flora in mice with colon cancer
"highlight2" >other↝, The effect of BBR on inflammatory cytokines, including IL-6, FGF, and PDGF, was not obvious
"highlight2" >IL10↓, BBR significantly downregulated IL-10 levels (P < 0.05) and reduced c-Myc, DNMT1, and DNMT3B
"highlight2" >cMyc↓,
"highlight2" >DNMT1↓,
"highlight2" >DNMTs↓,

2711- BBR,    Berberine inhibits the progression of breast cancer by regulating METTL3-mediated m6A modification of FGF7 mRNA
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
"highlight2" >TumCP↓, BBR treatment hindered breast cancer cell proliferation, invasion, migration, and induced apoptosis
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >Apoptosis↑,
"highlight2" >FGF↓, FGF7 expression was upregulated in breast cancer tissues, while its level was reduced in BBR-treated tumor cells
"highlight2" >IGFBP3↑, IGF2BP3 recognized the m6A modification of FGF7 mRNA and enhanced its expression

2710- BBR,    Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells
- in-vitro, Ovarian, SKOV3
"highlight2" >Warburg↓, berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly.
"highlight2" >miR-145↑,
"highlight2" >HK2↓, westernblot suggested that berberine could significantly down regulate the expression of HK2
"highlight2" >TET3↑, Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene.
"highlight2" >Glycolysis↓, Furthermore, the effect of berberine on glycolysis related enzymes was detected, the results of qRT-PCR and westernblot suggested that berberine could significantly down regulate the expression of HK2
"highlight2" >PKM2↓, Western blot results showed down-expression of miR-145 reversed berberine's inhibition of HK2 expression. PKM2, pyruvate kinase M2; HK2, Hexokinase2; GLUT1, glucose transporter 1; LDH, lactate dehydrogenase; PFK2, phosphofructokinase 2; PDK1,
"highlight2" >GLUT1↓,
"highlight2" >LDH↓,
"highlight2" >PFK2↓,
"highlight2" >PDK1↓,

2709- BBR,    Berberine inhibits the glycolysis and proliferation of hepatocellular carcinoma cells by down-regulating HIF-1α
- in-vitro, HCC, HepG2
"highlight2" >TumCP↓, After exposure to 100 μmol/L BBR, the proliferation, migration and invasion of HepG2 cells were reduced, along with apoptosis was increased, while the levels of glycolysis-related proteins were decreased
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >Apoptosis↑,
"highlight2" >Glycolysis↓, BBR inhibits proliferation and glycolysis of HCC cells in vivo
"highlight2" >Hif1a↓, BBR can down-regulate HIF-1α in the hypoxic microenvironment, and hinder the proliferation and metastasis of breast cancer cell
"highlight2" >GLUT1↓, treatment with 100μmol/L BBR for 48 h, the levels of GLUT1, HK2, PKM2, and LDHA mRNA were markedly reduced in HepG2 cells
"highlight2" >HK2↓,
"highlight2" >PKM2↓,
"highlight2" >LDHA↓,

2708- BBR,    Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells
- in-vitro, CRC, HCT116
"highlight2" >TumCG↓, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines
"highlight2" >GlucoseCon↓,
"highlight2" >GLUT1↓,
"highlight2" >LDHA↓, berberine inhibited the mRNA levels of LDHA and HK2 in a concentration-dependent manner
"highlight2" >HK2↓,
"highlight2" >Hif1a↓, protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines
"highlight2" >mTOR↓, mTOR signaling previously reported to regulate HIF‑1α protein synthesis was further found to be suppressed by berberine.
"highlight2" >Glycolysis↓, berberine inhibits overactive glucose metabolism of colon cancer cells via suppressing mTOR‑depended HIF‑1α protein synthesis

1378- BBR,    Berberine induces non-small cell lung cancer apoptosis via the activation of the ROS/ASK1/JNK pathway
- in-vitro, Lung, NA
"highlight2" >Apoptosis↑,
"highlight2" >Casp3↑,
"highlight2" >Cyt‑c↑, cytochrome c release
"highlight2" >MMP↓,
"highlight2" >p‑JNK↑,
"highlight2" >eff↓, N-acetyl cysteine (NAC), a ROS scavenger, was sufficient to both suppress apoptosis signal-regulating kinase 1 (ASK1) and JNK activation and disrupt apoptotic induction.

7- BBR,    Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth
- vitro+vivo, MB, NA
"highlight2" >HH↓,
"highlight2" >Gli1↓,
"highlight2" >PTCH1↓,
"highlight2" >Smo↓,

1392- BBR,    Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress
- in-vitro, GC, AGS - in-vitro, GC, MKN45
"highlight2" >TumCG↓,
"highlight2" >TumCMig↓,
"highlight2" >ROS↑, intracellular
"highlight2" >MDA↑, intracellular
"highlight2" >SOD↓, intracellular
"highlight2" >NRF2↓,
"highlight2" >HO-1↓,
"highlight2" >Hif1a↓,
"highlight2" >EMT↓,
"highlight2" >Snail↓,
"highlight2" >Vim↓,

1390- BBR,  Rad,    Berberine Inhibited Radioresistant Effects and Enhanced Anti-Tumor Effects in the Irradiated-Human Prostate Cancer Cells
- in-vitro, Pca, PC3
"highlight2" >RadioS↑, cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑, ROS generation was elevated by berberine with or without irradiation.
"highlight2" >eff↑, antioxidant NAC inhibited berberine and radiation-induced cell death.
"highlight2" >BAX↑,
"highlight2" >Casp3↑,
"highlight2" >P53↑,
"highlight2" >p38↑,
"highlight2" >JNK↑,
"highlight2" >Bcl-2↓,
"highlight2" >ERK↓,
"highlight2" >HO-1↓,

1389- BBR,  Lap,    Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS
- in-vitro, BC, BT474 - in-vitro, BC, AU-565
"highlight2" >ChemoSen↑, combination therapy of berberine with lapatinib overcame lapatinib resistance.
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑,
"highlight2" >NRF2↓, Berberine reverses lapatinib resistance by inhibiting the Nrf2 signaling pathway

1387- BBR,    Antitumor Activity of Berberine by Activating Autophagy and Apoptosis in CAL-62 and BHT-101 Anaplastic Thyroid Carcinoma Cell Lines
- in-vitro, Thyroid, CAL-62
"highlight2" >TumCG↓,
"highlight2" >Apoptosis↑,
"highlight2" >LC3B↑, LC3B-II
"highlight2" >ROS↑,
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >mTOR↓,

1386- BBR,    Berberine-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
"highlight2" >tumCV↓,
"highlight2" >ROS↑,
"highlight2" >JNK↑,
"highlight2" >MMP↓,
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,
"highlight2" >Cyt‑c↑, increased the release of cytochrome c
"highlight2" >AIF↝,

1385- BBR,  5-FU,    Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
"highlight2" >eff↓, Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents
"highlight2" >ROS↑, LDB mildly while HDB greatly stimulated ROS generation BBR-induced ROS generation may activate the antioxidant response therefore to promote cancer cell proliferation.
"highlight2" >TumCP↑,
"highlight2" >NRF2↑,
"highlight2" >ChemoSen↓, These findings revealed a potential negative impact of BBR on its adjuvant anti-breast cancer therapy

1384- BBR,    Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines
- in-vitro, PC, PANC1
"highlight2" >TumCCA↑, inducing G1-phase arrest
"highlight2" >ROS↑, In cells treated with 10 µM berberine, ROS production increased 2.6-fold relative to control cells
"highlight2" >Apoptosis↑,

1382- BBR,    Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells
- in-vitro, Melanoma, SK-MEL-28
"highlight2" >Apoptosis↑,
"highlight2" >necrosis↑,
"highlight2" >DNAdam↑, increase in the DNA damage index
"highlight2" >TumCCA↑, G1/G0 phase
"highlight2" >ROS↑, The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels
"highlight2" >Casp3↑,
"highlight2" >p‑P53↑,
"highlight2" >ERK↑, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls.

1381- BBR,  Rad,    Berberine enhances the sensitivity of radiotherapy in ovarian cancer cell line (SKOV-3)
- in-vitro, Ovarian, SKOV3
"highlight2" >RadioS↑, berberine might be a capable radiosensitizer for treating SKOV-3, because of oxidative DNA damage
"highlight2" >ROS↑,
"highlight2" >GSH↓, decreased level of (GSH) content supported the elevated ROS generation data
"highlight2" >Apoptosis↑,

1380- BBR,  doxoR,    treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.
- in-vivo, Nor, NA
"highlight2" >*ROS↓, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts.
"highlight2" >*MDA↓, Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs.
"highlight2" >*SOD↑,
"highlight2" >*NRF2↑,
"highlight2" >*HO-1↑,

1379- BBR,    Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells
- in-vitro, lymphoma, NA
"highlight2" >TumCP↓,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,
"highlight2" >cycD1↓,
"highlight2" >TumCCA↑, G0/G1 phase
"highlight2" >MMP↓,
"highlight2" >Ca+2↑,
"highlight2" >ATP↓, decreased intracellular adenosine triphosphate production,
"highlight2" >mtDam↑, mitochondrial dysfunction
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑,
"highlight2" >JNK↑,
"highlight2" >eff↓, treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358.

1393- BBR,  EPI,    Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest
- in-vitro, Bladder, T24
"highlight2" >ChemoSen↑, Ber enhanced the inhibitory effect of EPI on the viability of T24 cells
"highlight2" >TumCCA↑, cycle arrest at G0/G1
"highlight2" >Apoptosis↑,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >BAX↑,
"highlight2" >P53↑,
"highlight2" >P21↑,
"highlight2" >Bcl-2↓,
"highlight2" >ROS↑, Ber significantly increased ROS production

1377- BBR,    Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway
- in-vitro, Arthritis, NA
"highlight2" >Apoptosis↑, 30 μmol/L
"highlight2" >MMP↓,
"highlight2" >Bax:Bcl2↑,
"highlight2" >LC3‑Ⅱ/LC3‑Ⅰ↓, Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01)
"highlight2" >p62↑,
"highlight2" >*ROS↓,

1376- BBR,  immuno,    Berberine sensitizes immune checkpoint blockade therapy in melanoma by NQO1 inhibition and ROS activation
- in-vivo, Melanoma, NA
"highlight2" >OS↑, BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice.
"highlight2" >ROS↑,
"highlight2" >NQO1↓,
"highlight2" >ICD↑,

1375- BBR,    13-[CH2CO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein
- in-vitro, CRC, HCT8 - in-vivo, NA, NA
"highlight2" >ROS↑,
"highlight2" >TumCP↓, 2-5X lower IC50 than normal BBR
"highlight2" >XIAP↓,
"highlight2" >TumCG↓,
"highlight2" >*toxicity↓, 13-Cys-BBR Had No Kidney And Liver Toxicity

1374- BBR,  PDT,    Berberine associated photodynamic therapy promotes autophagy and apoptosis via ROS generation in renal carcinoma cells
- in-vitro, RCC, 786-O - in-vitro, RCC, HK-2
"highlight2" >ROS↑,
"highlight2" >TumAuto↑,
"highlight2" >Apoptosis↑,
"highlight2" >Casp3↑,
"highlight2" >eff↑, HK-2 treated with BBR associated with PDT showed a significant decrease in the cellular viability compared to the control cells

1299- BBR,    Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review
- Review, NA, NA
"highlight2" >TumCCA↑, G1 phase, G0/G1 phase, or G2/M phase
"highlight2" >TP53↑,
"highlight2" >COX2↓,
"highlight2" >Bax:Bcl2↑,
"highlight2" >ROS↑,
"highlight2" >VEGFR2↓,
"highlight2" >Akt↓,
"highlight2" >ERK↓,
"highlight2" >MMP2↓, Berberine also decreased MMP-2, MMP-9, E-cadherin, EGF, bFGF, and fibronectin in the breast cancer cells.
"highlight2" >MMP9↓,
"highlight2" >IL8↑,
"highlight2" >P21↑,
"highlight2" >p27↑,
"highlight2" >E-cadherin↓,
"highlight2" >Fibronectin↓,
"highlight2" >cMyc↓, The results indicated that these derivatives could selectively induce and stabilize the formation of the c-myc in the parallel molecular G-quadruplex. Accordingly, transcription of c-myc was down-regulated in the cancer cell line

1102- BBR,    Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARα/RARβ in melanoma cells
- in-vitro, Melanoma, B16-BL6
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >EMT↓,
"highlight2" >p‑PI3K↓,
"highlight2" >p‑Akt↓,
"highlight2" >RARα↓,
"highlight2" >RARβ↑,
"highlight2" >RARγ↑,
"highlight2" >E-cadherin↑,
"highlight2" >N-cadherin↓,

1092- BBR,    Berberine as a Potential Anticancer Agent: A Comprehensive Review
- Review, NA, NA
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑,
"highlight2" >TumAuto↑,
"highlight2" >TumCI↓,
"highlight2" >IL1↓, IL-1α, IL-1β
"highlight2" >IL6↓,
"highlight2" >TNF-α↓,
"highlight2" >LDH↓, BBR also increases the release of Lactic Acid Dehydrogenase (LDH) in the MDA epithelial human breast cancer cell line (MDA-cells)
"highlight2" >P2X7↓,
"highlight2" >proCasp1↓,
"highlight2" >Casp1↓,
"highlight2" >ASC↓,

1030- BBR,    Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5
- in-vitro, Lung, H460
"highlight2" >PD-L1↓,
"highlight2" >TumCG↓,
"highlight2" >Ki-67↓,
"highlight2" >cl‑Casp3↑,

1010- BBR,    Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells
- vitro+vivo, CRC, NA
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >TumCG↓,

956- BBR,    Berberine inhibits HIF-1alpha expression via enhanced proteolysis
- in-vitro, Nor, HUVECs - in-vitro, GC, SCM1
"highlight2" >Hif1a↓, did not down-regulate HIF-1alpha mRNA but destabilized HIF-1alpha protein
"highlight2" >angioG↓,

940- BBR,    Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression
- vitro+vivo, PC, PANC1 - in-vivo, PC, MIA PaCa-2
"highlight2" >LDHA↓, berberine was selected as functional inhibitor of LDHA
"highlight2" >lactateProd↓, berberine treatment significantly suppressed intracellular lactate content at 5 μΜ and 10 μΜ
"highlight2" >AMPKα↓, suppressed AMPKa activation
"highlight2" >TumVol↓,
"highlight2" >Ki-67↓,

932- BBR,    The short-term effects of berberine in the liver: Narrow margins between benefits and toxicity
- in-vivo, Nor, NA
"highlight2" >*glucoNG↓, These results can be regarded as evidence that the direct inhibitory effects of berberine on gluconeogenesis
"highlight2" >*Glycolysis↑,
"highlight2" >*NH3↑, inhibited ammonia detoxification
"highlight2" >*NADPH/NADP+↑,
"highlight2" >*ATP↓,
"highlight2" >*toxicity↑, narrow margin between the expected benefits and toxicity

2021- BBR,    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways
- Review, NA, NA
"highlight2" >*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
"highlight2" >*Inflam↓,
"highlight2" >Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
"highlight2" >TumCCA↑,
"highlight2" >BAX↑,
"highlight2" >eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
"highlight2" >VEGF↓, berberine also prevented the expression of VEGF
"highlight2" >PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
"highlight2" >β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
"highlight2" >Wnt↓,
"highlight2" >EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
"highlight2" >AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
"highlight2" >NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
"highlight2" >COX2↑,
"highlight2" >NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
"highlight2" >RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
"highlight2" >STAT3↓, regulating the JAK–STAT3 signaling pathway
"highlight2" >ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
"highlight2" >AR↓, Berberine reduced the androgen receptor transcriptional activity
"highlight2" >ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
"highlight2" >eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
"highlight2" >selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
"highlight2" >selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
"highlight2" >BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
"highlight2" >DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
"highlight2" >cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc

2677- BBR,    Liposome-Encapsulated Berberine Alleviates Liver Injury in Type 2 Diabetes via Promoting AMPK/mTOR-Mediated Autophagy and Reducing ER Stress: Morphometric and Immunohistochemical Scoring
- in-vivo, Diabetic, NA
"highlight2" >*hepatoP↑, berberine (Lip-BBR) to aid in ameliorating hepatic damage and steatosis, insulin homeostasis, and regulating lipid metabolism in type 2 diabetes (T2DM)
"highlight2" >*LC3II↑, Lip-BBR treatment promoted autophagy via the activation of LC3-II and Bclin-1 proteins and activated the AMPK/mTOR pathway in the liver tissue of T2DM rats.
"highlight2" >*Beclin-1↑,
"highlight2" >*AMPK↑,
"highlight2" >*mTOR↑,
"highlight2" >*ER Stress↓, It decreased the endoplasmic reticulum stress by limiting the CHOP, JNK expression, oxidative stress, and inflammation.
"highlight2" >*CHOP↓,
"highlight2" >*JNK↓,
"highlight2" >*ROS↓,
"highlight2" >*Inflam↓,
"highlight2" >*BG↓, Oral supplementation of diabetic rats either by Lip-BBR or Vild, 10 mg/kg of each, significantly (p < 0.001) lowered the blood glucose levels of tested diabetic rats compared to the diabetic group.
"highlight2" >*SOD↑, when the diabetic rats received Lip-BBR, the decrements were less pronounced compared to the diabetic group by 1.16 fold, 2.52 fold, and 67.57% for SOD, GPX, and CAT, respectively.
"highlight2" >*GPx↑,
"highlight2" >*Catalase↑,
"highlight2" >*IL10↑, Treatment of the diabetic rats with Lip-BBR significantly (p < 0.001) elevated serum IL-10 levels by 37.01% compared with diabetic rats.
"highlight2" >*IL6↓, Oral supplementation of Lip-BBR could markedly (p < 0.0001) reduce the elevated serum levels of IL-6 and TNF-α when it is used as a single treatment by 55.83% and 49.54%,
"highlight2" >*TNF-α↓,
"highlight2" >*ALAT↓, ALT, AST, and ALP in the diabetic group were significantly higher (p < 0.0001) by 88.95%, 81.64%, and 1.8 fold, respectively, compared with those in the control group, but this was reversed by the treatment with Lip-BBR
"highlight2" >*AST↓,
"highlight2" >*ALP↓,

2676- BBR,    Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress
- in-vivo, Nor, NA - in-vivo, CardioV, NA
"highlight2" >*cardioP↑, Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage.
"highlight2" >*ROS↓,
"highlight2" >*ER Stress↓, pretreatment with BBR suppressed MI/R-induced ER stress
"highlight2" >*p‑PERK↓, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues.
"highlight2" >*p‑eIF2α↓,
"highlight2" >*ATF4↓,
"highlight2" >CHOP↓,
"highlight2" >*JAK2↑, Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues
"highlight2" >*STAT3↑,
"highlight2" >*UPR↓, Therefore, reducing excessive UPR, also referred to as ER stress, is of great importance in ameliorating MI/R injury.

2675- BBR,    The therapeutic effects of berberine against different diseases: A review on the involvement of the endoplasmic reticulum stress
- Review, Var, NA
"highlight2" >*Inflam↓, including anti-inflammatory, antioxidative, anti-apoptotic, antiproliferative, and antihypertensive.
"highlight2" >*antiOx↑,
"highlight2" >*ER Stress↓, BBR can decrease apoptosis and inflammation following different pathological conditions, which might be mediated by targeting ER stress pathways.
"highlight2" >*cardioP↑, protective potential of BBR against several diseases, such as metabolic disorders, cancer, intestinal diseases, cardiovascular, liver, kidney, and central nervous system diseases, in both in vivo and in vitro studies.
"highlight2" >*RenoP↑,
"highlight2" >*hepatoP↑,

2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
"highlight2" >Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
"highlight2" >AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
"highlight2" >Apoptosis↑,
"highlight2" >TumAuto↑,
"highlight2" >TumCCA↑,
"highlight2" >TumMeta↓,
"highlight2" >TumCI↓,
"highlight2" >eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
"highlight2" >eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
"highlight2" >CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
"highlight2" >TNF-α↓,
"highlight2" >IL1↓,
"highlight2" >BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
"highlight2" >BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
"highlight2" >other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
"highlight2" >AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
"highlight2" >MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
"highlight2" >NF-kB↓,
"highlight2" >IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
"highlight2" >MCP1↓,
"highlight2" >PGE2↓,
"highlight2" >COX2↓,
"highlight2" >*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
"highlight2" >*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
"highlight2" >*GPx↑,
"highlight2" >*Catalase↑,
"highlight2" >AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
"highlight2" >TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
"highlight2" >angioG↓,
"highlight2" >Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
"highlight2" >FasL↑,
"highlight2" >ROS↑,
"highlight2" >ATM↑,
"highlight2" >P53↑,
"highlight2" >RB1↑,
"highlight2" >Casp9↑,
"highlight2" >Casp8↑,
"highlight2" >Casp3↓,
"highlight2" >BAX↑,
"highlight2" >Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
"highlight2" >Bcl-xL↓,
"highlight2" >IAP1↓,
"highlight2" >XIAP↓,
"highlight2" >survivin↓,
"highlight2" >MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
"highlight2" >MMP9↓,
"highlight2" >CycB↓, Inhibition of cyclin B1, cdc2, cdc25c
"highlight2" >CDC25↓,
"highlight2" >CDC25↓,
"highlight2" >Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
"highlight2" >MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
"highlight2" >RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
"highlight2" >mTOR↓, U87 cell, Inhibition of m-TOR signaling
"highlight2" >MDM2↓, Downregulation of MDM2
"highlight2" >LC3II↑, Increase of LC3-II and beclin-1
"highlight2" >ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
"highlight2" >COX2↓,
"highlight2" >MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
"highlight2" >TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
"highlight2" >EMT↑,
"highlight2" >ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
"highlight2" >FAK↓,
"highlight2" >RAS↓,
"highlight2" >Rho↓,
"highlight2" >NF-kB↓,
"highlight2" >uPA↓,
"highlight2" >MMP1↓,
"highlight2" >MMP13↓,
"highlight2" >ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents

2673- BBR,    Therapeutic potential and recent delivery systems of berberine: A wonder molecule
- Review, Var, NA
"highlight2" >*BioAv↓, clinical use of berberine has been limited due to its poor intestinal absorption, low bioavailability and limited penetration.
"highlight2" >*Half-Life↓, t1/2, Cmax and AUC observed in healthy human male volunteers after single dose administration of 300 mg orally and their values have been reported to be 0.87 ± 0.03 h, 394.7 ± 155.4 µg/L and 2799.0 ± 1128.5 µg/L respectively
"highlight2" >*neuroP↑, neuroprotective action have been investigated determining enhanced blood brain barrier (BBB) penetrability
"highlight2" >BBB↑,
"highlight2" >toxicity↓, These also dole out in low cost, seldom side effects and easy availability.

2672- BBR,    The anti-aging mechanism of Berberine associated with metabolic control
- Review, Var, NA
"highlight2" >*BioAv↝, The chemical compound salt form of Ber includes hydrochloride, sulfate, and phosphate with various water solubilities. For example, hydrochloride salt is less soluble in water, whereas sulfate and phosphate salts are relatively water-soluble.
"highlight2" >*BioAv↝, Meanwhile, chloride or sulfate of Ber is commonly used as an over-the-counter (OTC), orally administered drug for clinical purposes
"highlight2" >*BioAv↝, After oral administration, Ber is transformed into different phase I metabolites, including berberrubine, thalifendine, demethyleneberberine, and jatrorrhizine, in the liver by cytochrome P450 enzymes (CYPs)
"highlight2" >*Half-Life↓, A rapid elimination half-life about 0.22h has been observed in plasma, whereas a slow elimination half-life about 12h in the hippocampus was observed after intravenous administration in rats.

2671- BBR,    Berberine and Its More Biologically Available Derivative, Dihydroberberine, Inhibit Mitochondrial Respiratory Complex I: A Mechanism for the Action of Berberine to Activate AMP-Activated Protein Kinase and Improve Insulin Action
- in-vivo, Diabetic, NA
"highlight2" >*BioAv↓, After oral administration of 20 mg/kg BBR, we were unable to detect BBR in the plasma
"highlight2" >*Half-Life↝, In contrast, dhBBR at the same oral dose was rapidly detected in the plasma (Supplementary Fig. 2), displaying a half-life (t1/2) of 3.5 ± 1.3 h and a maximum concentration (Cmax) of 2.8 ± 0.5 ng/ml
"highlight2" >*OCR↓, BBR produced a dose-dependent inhibition of oxygen consumption in isolated muscle mitochondria with complex I–linked substrate (pyruvate),
"highlight2" >*AMPK↑, ability of BBR to activate AMPK

2670- BBR,    Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
- Review, Var, NA
"highlight2" >*Inflam↓, According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity
"highlight2" >*antiOx↑,
"highlight2" >*Ca+2↓, Impaired cerebral arterial vasodilation can be alleviated by berberine in a diabetic rat model via down-regulation of the intracellular Ca2+ processing of VSMCs
"highlight2" >*BioAv↓, poor oral absorption and low bioavailability
"highlight2" >*BioAv↑, Conversion of biological small molecules into salt compounds may be a method to improve its bioavailability in vivo.
"highlight2" >*BioAv↑, Long-chain alkylation (C5-C9) may enhance hydrophobicity, which has been shown to improve bioavailability; for example, 9-O-benzylation further enhances lipophilicity and imparts neuroprotective effect
"highlight2" >*angioG↑, figure 2
"highlight2" >*MAPK↓,
"highlight2" >*AMPK↓, 100 mg/kg berberine daily for 14 days attenuated ischemia–reperfusion injury via hemodynamic improvements and inhibition of AMPK activity in both non-ischemic and ischemic areas of rat heart tissue
"highlight2" >*NF-kB↓,
"highlight2" >VEGF↓,
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >MMP2↓,
"highlight2" >Bcl-2↓,
"highlight2" >ERK↓,

2337- BBR,    Berberine Inhibited the Proliferation of Cancer Cells by Suppressing the Activity of Tumor Pyruvate Kinase M2
- in-vitro, CRC, HCT116 - in-vitro, Cerv, HeLa
"highlight2" >TumCP↓, berberine showed antitumor activity of HCT-116 and HeLa cells with the suppression of cell proliferation
"highlight2" >PKM2↓, berberine inhibited the enzyme activity of PKM2 in cancer cells, but had no impact on PKM2 expression.

2336- BBR,    Berberine Targets PKM2 to Activate the t-PA-Induced Fibrinolytic System and Improves Thrombosis
- in-vivo, Nor, NA
"highlight2" >*PKM2↓, PKM2 was suppressed following BBR administration,

2335- BBR,    Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer
- in-vitro, CRC, HT29 - in-vitro, CRC, HCT116 - in-vivo, NA, NA
"highlight2" >PKM2↓, berberine is directly bound to pyruvate kinase isozyme type M2 (PKM2) in colorectal cancer cells. Berberine inhibited PKM2 activity
"highlight2" >Glycolysis↓, berberine was shown to inhibit the reprogramming of glucose metabolism and the phosphorylation of STAT3, down regulate the expression of Bcl-2 and Cyclin D1 genes
"highlight2" >p‑STAT3↓,
"highlight2" >Bcl-2↓,
"highlight2" >cycD1↓,
"highlight2" >TumCG↓, n vivo experiments showed that tumor growth was inhibited in HT29 cell-bearing mice injected intraperitoneally with berberine (5 or 10 mg/kg body weight)
"highlight2" >Ki-67↓, Berberine inhibited the proliferation index (Ki67 expression)
"highlight2" >lactateProd↓, Berberine inhibited lactate production, glucose uptake, pyruvate production, and PKM2 activity in HWT tumor tissues, but no apparent effects were observed in both F244A mutant cells and I199S mutant tumor tissues
"highlight2" >glucose↓,

2023- BBR,    Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor
- in-vitro, Colon, NA - in-vitro, Nor, YAMC
"highlight2" >TumCD↑, Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells.
"highlight2" >*toxicity↓, In contrast, YAMC(normal) cells were not sensitive to berberine-induced cell death. less cytotoxic effects on normal colon epithelial cells.
"highlight2" >selectivity↑, see figure 2
"highlight2" >ROS↑, berberine-stimulated ROS production
"highlight2" >*ROS∅, ROS production in a concentration-dependent manner only in IMCE cells, but not in YAMC cells. In YAMC cells, berberine did not induce ROS production
"highlight2" >MMP↓, berberine induced mitochondrial depolarization in a concentration-dependent manner in IMCE cells, but not in YAMC cells
"highlight2" >*MMP∅, but not in YAMC cells
"highlight2" >PARP↑, Berberine Activation of PARP
"highlight2" >BioAv↝, absorption of berberine by YAMC is lower than that by IMCE cells

2022- BBR,  GoldNP,  Rad,    Berberine-loaded Janus gold mesoporous silica nanocarriers for chemo/radio/photothermal therapy of liver cancer and radiation-induced injury inhibition
- in-vitro, Liver, SMMC-7721 cell - in-vitro, Nor, HL7702
"highlight2" >*toxicity↓, Berberine (Ber), an isoquinolin alkaloid with low toxicity and protective effects against radiotherapy
"highlight2" >radioP↑,
"highlight2" >BioAv↑, We preloaded Ber into folic acid targeting Janus gold mesoporous silica nanocarriers (FA-JGMSNs) for overcoming the poor bioavailability of Ber.
"highlight2" >AntiTum↑, highly efficient anti-tumor effect, good biosafety
"highlight2" >selectivity↑, as well as the effective protection of normal tissue of this nanoplatform.
"highlight2" >eff↑, These selective distributions of Ber in cancer cells and normal cells originated from selective endocytosis as well as pH-responsive drug release, which were conducive to achieving an improved therapeutic effect of Ber.
"highlight2" >chemoP↑, Notably, chemo/radio/photothermal therapeutics didn’t cause the amounts of deaths of HL-7702 cells, indicating an excellent biosafety of the triple-model therapy.

1394- BBR,  DL,    Synergistic Inhibitory Effect of Berberine and d-Limonene on Human Gastric Carcinoma Cell Line MGC803
- in-vitro, GC, MGC803
"highlight2" >eff↑, Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >Casp3↑,
"highlight2" >Bcl-2↓,
"highlight2" >TumCCA↑,

1405- BBR,  Chit,    Chitosan/alginate nanogel potentiate berberine uptake and enhance oxidative stress mediated apoptotic cell death in HepG2 cells
- in-vitro, Liver, HepG2
"highlight2" >*BioAv↑, we reported to develop a hydrophilic nanogel (NG) composed of Chitosan (Chi) and sodium alginate (Alg) using the ion gelation method for delivering Berberine hydrochloride (BBR),
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >TumCP↓,

1404- BBR,    Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation
- in-vitro, Pca, PC3
"highlight2" >Apoptosis↑,
"highlight2" >*Apoptosis∅, not seen in non-neoplastic human prostate epithelial cells (PWR-1E)
"highlight2" >MMP↓,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >ROS↑,
"highlight2" >eff↓, Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells.
"highlight2" >Cyt‑c↑, release of cytochrome c

1402- BBR,    Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction
- in-vitro, GBM, T98G
"highlight2" >tumCV↓,
"highlight2" >ROS↑,
"highlight2" >Ca+2↑,
"highlight2" >ER Stress↑,
"highlight2" >eff↓, administration of the antioxidants, N-acetylcysteine and glutathione, reversed berberine-induced apoptosis
"highlight2" >Bax:Bcl2↑,
"highlight2" >MMP↓,
"highlight2" >Casp9↑,
"highlight2" >Casp3↑,
"highlight2" >cl‑PARP↑,

1401- BBR,    Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity
- in-vitro, GBM, U87MG
"highlight2" >TumCP↓, 25 µM of 24 h
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑, BBR (25 μM/24 h) increased oxidative stress in U87MG cells

1400- BBR,    Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells
- in-vitro, Melanoma, U266
"highlight2" >ROS↑,
"highlight2" >TumCCA↑, G2/M phase arrest
"highlight2" >Apoptosis↑,
"highlight2" >miR-21↓,
"highlight2" >Bcl-2↓,
"highlight2" >NF-kB↓, 80 μmol/L
"highlight2" >Set9↑, 2 fold

1399- BBR,  Rad,    Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review
- Review, NA, NA
"highlight2" >*ROS↓, normal cells
"highlight2" >*MDA↓, normal cells
"highlight2" >*TNF-α↓, normal cells
"highlight2" >*TGF-β↓, TGF-β1 normal cells
"highlight2" >*IL10↑, normal cells
"highlight2" >ROS↑, cancer cells
"highlight2" >DNAdam↑, cancer cells
"highlight2" >mtDam↑, cancer cells
"highlight2" >MMP↓, cancer cells
"highlight2" >Apoptosis↑, cancer cells
"highlight2" >TumCCA↑, cancer cells
"highlight2" >Hif1a↓, cancer cells
"highlight2" >VEGF↓, cancer cells
"highlight2" >RadioS↑, revealed radiosensitizing properties

1398- BBR,    Berberine inhibits the progression of renal cell carcinoma cells by regulating reactive oxygen species generation and inducing DNA damage
- in-vitro, Kidney, NA
"highlight2" >TumCP↓,
"highlight2" >TumCMig↓,
"highlight2" >ROS↑,
"highlight2" >Apoptosis↑,
"highlight2" >BAX↑,
"highlight2" >BAD↑,
"highlight2" >Bak↑,
"highlight2" >Cyt‑c↑,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >E-cadherin↑,
"highlight2" >TIMP1↑,
"highlight2" >γH2AX↑,
"highlight2" >Bcl-2↓,
"highlight2" >N-cadherin↓,
"highlight2" >Vim↓,
"highlight2" >Snail↓,
"highlight2" >RAD51↓,
"highlight2" >PCNA↓,

1397- BBR,  Chemo,    Effects of Coptis extract combined with chemotherapeutic agents on ROS production, multidrug resistance, and cell growth in A549 human lung cancer cells
- in-vitro, Lung, A549
"highlight2" >TumCG↓,
"highlight2" >ROS↑, COP and BER increased ROS production and reduced MDR in A549 cells.
"highlight2" >MDR1↓, reduce MDR

1396- BBR,    Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro
- in-vitro, GC, SNU1041 - in-vitro, GC, SNU5
"highlight2" >tumCV↓,
"highlight2" >ROS↑,
"highlight2" >MMP1↓, berberine induced downregulation of MMP-1 -2, and -9 but did not affect the level of MMP-7
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >MMP7∅,

1395- BBR,    Analysis of the mechanism of berberine against stomach carcinoma based on network pharmacology and experimental validation
- in-vitro, GC, NA
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >ATP↓,
"highlight2" >AMPK↑,
"highlight2" >TP53↑,
"highlight2" >p‑MAPK↓, decreased phosphorylated-MAPK3/1 expression
"highlight2" >p‑ERK↓,

1383- CUR,  BBR,  RES,    Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases
- Review, NA, NA
"highlight2" >GSK‐3β↝,
"highlight2" >ROS↑, BBB increased ROS production by decreasing c-MYC expression

3796- QC,  BBR,    Biomarker discovery and phytochemical interventions in Alzheimer's disease: A path to therapeutic advances
- Review, AD, NA
"highlight2" >*CDK5↓, BAD, CDK5, FN1, ITGA4, and MAPK9 were identified. Quercetin and Berberine have shown significant binding affinities to these biomarkers

1391- RES,  BBR,    Effects of Resveratrol, Berberine and Their Combinations on Reactive Oxygen Species, Survival and Apoptosis in Human Squamous Carcinoma (SCC-25) Cells
- in-vitro, Tong, SCC25
"highlight2" >ROS↑,
"highlight2" >eff↑, cytotoxicity of the compounds was significantly improved after their combined application Additive effects were observed for doses lower than the calculated IC50 of berberine [IC50=23µg/ml] and resveratrol [IC50=9µg/ml].

1403- SDT,  BBR,    From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells
- in-vitro, Cerv, HeLa - in-vitro, Lung, LLC1
"highlight2" >eff↑, revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability
"highlight2" >tumCV↓,
"highlight2" >ATP↓,
"highlight2" >ROS↑,
"highlight2" >Casp3↑,
"highlight2" >Casp7↑,
"highlight2" >mtDam↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 109

Results for Effect on Cancer/Diseased Cells:
AIF↝,1,   Akt↓,8,   p‑Akt↓,2,   AMPK↑,5,   AMPK↝,1,   AMPKα↓,1,   angioG↓,3,   AntiCan↑,1,   AntiTum↑,2,   AP-1↓,1,   APAF1↑,1,   Apoptosis↑,26,   AQPs↓,1,   AR↓,1,   ASC↓,1,   ATM↑,1,   ATP↓,5,   AXL↓,1,   BAD↑,2,   Bak↑,1,   BAX↑,7,   Bax:Bcl2↑,5,   BBB↑,1,   Bcl-2↓,10,   Bcl-xL↓,1,   BioAv↓,3,   BioAv↑,2,   BioAv↝,1,   Ca+2↑,2,   Casp↑,1,   Casp1↓,3,   proCasp1↓,1,   Casp3↓,1,   Casp3↑,10,   cl‑Casp3↑,5,   Casp7↑,2,   Casp8↑,3,   Casp9↑,5,   cl‑Casp9↑,3,   CCR7↓,1,   CD133↓,2,   CD4+↓,1,   CDC2↓,1,   CDC25↓,2,   CDK1↓,1,   CDK2↓,1,   CDK4↓,3,   CDK6↓,1,   chemoP↑,1,   ChemoSen↓,1,   ChemoSen↑,4,   CHOP↓,1,   CHOP↑,1,   cMyc↓,4,   COX2↓,6,   COX2↑,1,   CSCs↓,3,   CXCR4↓,1,   Cyc↓,1,   CycB↓,1,   cycD1↓,4,   cycE↓,2,   Cyt‑c↑,6,   Diff↓,1,   DNAdam↑,4,   DNMT1↓,3,   DNMT1↑,1,   DNMTs↓,1,   Dose?,1,   Dose↓,1,   Dose↑,1,   Dose↝,1,   E-cadherin↓,2,   E-cadherin↑,2,   eff↓,5,   eff↑,14,   eff↝,2,   EGFR↓,4,   p‑eIF2α↓,1,   EMT↓,4,   EMT↑,2,   ER Stress↑,4,   ERK↓,8,   ERK↑,2,   p‑ERK↓,1,   EZH2↓,2,   FAK↓,1,   Fas↑,1,   FasL↑,2,   FGF↓,1,   Fibronectin↓,1,   FOXO3↑,1,   Gli1↓,1,   GLS↓,1,   glucose↓,1,   GlucoseCon↓,2,   glut↓,1,   GLUT1↓,4,   Glycolysis↓,6,   GRP78/BiP↓,1,   GSH↓,1,   GSK‐3β↝,1,   GutMicro↑,2,   ac‑H3↑,1,   ac‑H4↑,1,   HDAC↓,3,   HDAC∅,1,   HH↓,1,   Hif1a↓,7,   HK2↓,3,   HO-1↓,2,   HSP70/HSPA5↓,1,   IAP1↓,1,   ICD↑,1,   IGF-1↓,1,   IGFBP3↑,1,   IL1↓,2,   IL10↓,1,   IL18↓,1,   IL1β↓,2,   IL6↓,3,   IL8↓,1,   IL8↑,1,   Inflam↓,3,   ITGB1↓,1,   JAK2↓,1,   p‑JAK2↓,1,   JNK↓,1,   JNK↑,3,   p‑JNK↑,1,   Ki-67↓,3,   lactateProd↓,2,   LC3‑Ⅱ/LC3‑Ⅰ↓,1,   LC3B↑,1,   LC3II↑,1,   LC3s↑,1,   LDH↓,2,   LDHA↓,3,   MAPK↓,2,   MAPK↑,2,   p‑MAPK↓,1,   MCP1↓,2,   MDA↑,1,   MDM2↓,1,   MDR1↓,1,   MEK↓,2,   miR-145↑,1,   miR-21↓,1,   MMP↓,14,   MMP1↓,2,   MMP13↓,1,   MMP2↓,9,   MMP3↓,1,   MMP7∅,1,   MMP9↓,8,   MMPs↓,1,   mtDam↑,3,   mTOR↓,7,   mTOR↝,1,   mTOR∅,1,   p‑mTOR↓,1,   p‑mTORC1↓,1,   N-cadherin?,1,   N-cadherin↓,2,   n-MYC↓,2,   NCAM↓,1,   necrosis↑,2,   Nestin↓,2,   NF-kB↓,4,   NOTCH↓,1,   NOTCH2↓,1,   NQO1↓,1,   NRF2↓,3,   NRF2↑,1,   OCT4↓,1,   OS↑,1,   other↓,1,   other↝,1,   P21↑,3,   p27↑,2,   P2X7↓,1,   p38↑,1,   p‑p38↑,1,   P53↑,4,   p‑P53↑,1,   p62↑,1,   PARP↑,2,   cl‑PARP↑,2,   PCNA↓,1,   PD-L1↓,1,   PDGF↓,1,   PDK1↓,2,   PERK↓,1,   p‑PERK↓,1,   PFK2↓,1,   PGE2↓,4,   PI3K↓,5,   p‑PI3K↓,1,   PKM2↓,4,   PPARγ↓,1,   PTCH1↓,1,   PTEN↑,2,   RAD51↓,1,   radioP↑,1,   RadioS↑,6,   Raf↓,1,   RARα↓,1,   RARβ↑,1,   RARγ↑,1,   RAS↓,1,   RB1↑,1,   RenoP↑,1,   Rho↓,1,   ROCK1↓,1,   ROS↑,36,   p‑S6K↓,1,   selectivity↑,7,   Set9↑,1,   SLC12A5↓,1,   Smo↓,1,   Snail↓,2,   SOD↓,1,   SOX2↓,3,   Sp1/3/4↓,1,   STAT3↓,2,   p‑STAT3↓,2,   survivin↓,1,   Telomerase↓,3,   TET3↑,1,   TGF-β↓,1,   TGF-β1↓,1,   TIMP1↑,1,   TNF-α↓,4,   toxicity↓,1,   TP53↑,2,   TumAuto↑,4,   TumCCA↑,19,   TumCD↑,2,   TumCG↓,11,   TumCI↓,10,   TumCMig↓,9,   TumCP↓,13,   TumCP↑,1,   tumCV↓,6,   TumMeta↓,1,   TumVol↓,1,   uPA↓,2,   VEGF↓,6,   VEGFR2↓,2,   Vim↓,2,   Warburg↓,2,   Wnt↓,1,   XIAP↓,2,   ac‑α-tubulin↑,1,   β-catenin/ZEB1↓,3,   γH2AX↑,1,  
Total Targets: 256

Results for Effect on Normal Cells:
5HT↑,1,   AChE↓,9,   Akt↓,1,   Akt↑,3,   p‑Akt↑,1,   ALAT↓,1,   ALP↓,1,   AMPK↓,1,   AMPK↑,2,   p‑AMPK↑,1,   angioG↑,2,   AntiAg↑,1,   antiOx?,1,   antiOx↓,1,   antiOx↑,11,   Apoptosis↓,3,   Apoptosis∅,1,   APP↓,4,   AST↓,1,   ATF4↓,1,   ATP↓,1,   Aβ↓,8,   BACE↓,3,   BAX↓,1,   BBB↑,3,   BChE?,1,   BChE↓,3,   BDNF↑,2,   Beclin-1↑,3,   BG↓,1,   BioAv↓,4,   BioAv↑,5,   BioAv↝,4,   Ca+2↓,2,   mt-Ca+2↓,1,   cardioP↑,6,   cl‑Casp3↓,1,   Catalase↑,2,   CD31↑,2,   CDK5↓,1,   CHOP↓,1,   cognitive↑,8,   CREB↑,1,   CRP↓,1,   DNAdam↓,1,   DNMT1↓,1,   DNMTs↓,1,   Dose↝,2,   eff↑,4,   eIF2α↓,1,   p‑eIF2α↓,1,   ER Stress↓,6,   ERK↑,1,   p‑ERK↑,2,   Ferroptosis↓,2,   FTH1↑,1,   glucoNG↓,1,   Glycolysis↑,1,   GPx↑,2,   GSH↑,3,   GSK‐3β↓,1,   GutMicro↑,1,   Half-Life↓,2,   Half-Life↝,2,   hepatoP↑,3,   HO-1↑,2,   HSP70/HSPA5↑,1,   HSP90↑,2,   IFN-γ↑,1,   IL10↑,4,   IL17↑,1,   IL1β↓,2,   IL6↓,2,   IL6↑,1,   Inflam↓,14,   JAK2↑,1,   JNK↓,3,   Jun↓,1,   KLF4↑,1,   LAMs↑,1,   LC3B↑,1,   LC3II↑,2,   LDL↓,2,   lipid-P↓,6,   MAOA↓,2,   MAOB↓,3,   MAPK↓,3,   MCU↓,1,   MDA↓,3,   memory↑,8,   MMP∅,1,   Mood↑,1,   motorD↑,1,   mTOR↓,1,   mTOR↑,1,   p‑mTOR↓,1,   N-cadherin↑,2,   NADPH/NADP+↑,1,   neuroP↑,9,   NF-kB↓,4,   NH3↑,1,   NRF2↑,2,   OCR↓,1,   other?,1,   p16↓,1,   p38↓,2,   p62↓,1,   P70S6K↓,2,   p‑PERK↓,1,   PI3K↓,1,   PI3K↑,1,   PKM2↓,1,   PP2A↑,1,   PPARγ↑,1,   RAD51↓,1,   RenoP↑,3,   RNS↓,1,   ROS↓,14,   ROS∅,1,   Smad1↑,1,   SOD↑,3,   STAT1↓,1,   STAT3↑,1,   STAT4↓,1,   tau?,1,   p‑tau↓,4,   TfR1/CD71↓,1,   TGF-β↓,1,   TGF-β1↓,1,   Th1 response↓,1,   Th17↓,1,   TNF-α↓,4,   toxicity↓,5,   toxicity↑,1,   TP53↑,1,   UPR↓,1,   VEGF↑,2,   α-SMA↓,1,  
Total Targets: 138

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:41  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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